Bufotenine and its derivatives: synthesis, analgesic effects identification and computational target prediction.
10.1016/S1875-5364(21)60044-4
- Author:
Chao ZHAO
1
;
Min CHEN
1
;
Shan-Liang SUN
1
;
Jiao-Jiao WANG
1
;
Yue ZHONG
1
;
Huan-Huan CHEN
1
;
He-Min LI
1
;
Han XU
1
;
Nian-Guang LI
2
;
Hong-Yue MA
3
;
Xiao-Long WANG
4
Author Information
1. National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing 210023, China.
2. National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address: linianguang@njucm.edu.cn.
3. National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address: hongyuema@njucm.edu.cn.
4. National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address: gregwang@njucm.edu.cn.
- Publication Type:Journal Article
- Keywords:
Analgesic;
Binding mode;
Bufotenine;
Reverse docking;
Target prediction
- From:
Chinese Journal of Natural Medicines (English Ed.)
2021;19(6):454-463
- CountryChina
- Language:English
-
Abstract:
Natural product bufotenine (5) which could be isolated from Venenum Bufonis, has been widely used as a tool in central nervous system (CNS) studies. We present here its quaternary ammonium salt (6) which was synthesized with high yields using 5-benzyloxyindole as raw materials, and we firstly discover its analgesic effects in vivo. The analgesic evaluation showed that compounds 5 and 6 had stronger effects on the behavior of formalin induced pain in mice. Moreover, the combination of compound 6 and morphine has a synergistic effect. We intended to explain the molecular mechanism of this effect. Therefore, 36 analgesic-related targets (including 15 G protein-coupled receptors, 6 enzymes, 13 ion channels, and 2 others) were systemically evaluated using reverse docking. The results indicate that bufotenine and its derivatives are closely related to acetyl cholinesterase (AChE) or α
